McNab, Jennifer A.

Abstract Only recently has the rodent hippocampus been implicated in orexigenic appetitive processing1,2. This function has been found to be mediated at least in part by lateral hypothalamic inputs involving an orexigenic neuropeptide, melanin-concentrating hormone3. This circuit remains elusive in humans. Here, we combine tractography, intracranial electrophysiology, cortico-subcortical evoked potentials, and brain-clearing 3D histology to identify an orexigenic circuit involving the lateral hypothalamus converging in a hippocampal subregion. We found that low-frequency power is modulated by sweet-fat food cues and this modulation was specific to the dorsolateral hippocampus. Lastly, structural and functional analyses of this circuit in a human cohort exhibiting dysregulated eating behavior revealed connectivity that was inversely related to body mass index. Collectively, this multimodal approach describes an orexigenic subnetwork within the human hippocampus implicated in obesity and related eating disorders.

PurposeWe investigate the importance of high gradient‐amplitude and high slew‐rate on oscillating gradient spin echo (OGSE) diffusion imaging for human brain imaging and evaluate human brain imaging with OGSE on the MAGNUS head‐gradient insert (200 mT/m amplitude and 500 T/m/s slew rate).MethodsSimulations with cosine‐modulated and trapezoidal‐cosine OGSE at various gradient amplitudes and slew rates were performed. Six healthy subjects were imaged with the MAGNUS gradient at 3T with OGSE at frequencies up to 100 Hz and b = 450 s/mm2. Comparisons were made against standard pulsed gradient spin echo (PGSE) diffusion in vivo and in an isotropic diffusion phantom.ResultsSimulations show that to achieve high frequency and b‐value simultaneously for OGSE, high gradient amplitude, high slew rates, and high peripheral nerve stimulation limits are required. A strong linear trend for increased diffusivity (mean: 8–19%, radial: 9–27%, parallel: 8–15%) was observed in normal white matter with OGSE (20 Hz to 100 Hz) as compared to PGSE. Linear fitting to frequency provided excellent correlation, and using a short‐range disorder model provided radial long‐term diffusivities of D∞,MD = 911 ± 72 µm2/s, D∞,PD = 1519 ± 164 µm2/s, and D∞,RD = 640 ± 111 µm2/s and correlation lengths of lc,MD = 0.802 ± 0.156 µm, lc,PD = 0.837 ± 0.172 µm, and lc,RD = 0.780 ± 0.174 µm. Diffusivity changes with OGSE frequency were negligible in the phantom, as expected.ConclusionThe high gradient amplitude, high slew rate, and high peripheral nerve stimulation thresholds of the MAGNUS head‐gradient enables OGSE acquisition for in vivo human brain imaging.